Elidel (Pimecrolimus) - Side Effects and Adverse Reactions

ADVERSE REACTIONS

No phototoxicity and no photoallergenicity were detected in clinical studies with 24 and 33 normal volunteers, respectively. In human dermal safety studies, ELIDEL ^® (pimecrolimus) Cream 1% did not induce contact sensitization or cumulative irritation.

      In a one-year safety study in pediatric patients age 2-17 years old involving sequential use of ELIDEL Cream and a topical corticosteroid, 43% of ELIDEL patients and 68% of vehicle patients used corticosteroids during the study. Corticosteroids were used for more than 7 days by 34% of ELIDEL patients and 54% of vehicle patients. An increased incidence of impetigo, skin infection, superinfection (infected atopic dermatitis), rhinitis, and urticaria were found in the patients that had used ELIDEL Cream and topical corticosteroid sequentially as compared to ELIDEL Cream alone.

      In 3 randomized, double-blind vehicle-controlled pediatric studies and one active-controlled adult study, 843 and 328 patients respectively, were treated with ELIDEL Cream. In these clinical trials, 48 (4%) of the 1,171 ELIDEL patients and 13 (3%) of 408 vehicle-treated patients discontinued therapy due to adverse events. Discontinuations for AEs were primarily due to application site reactions, and cutaneous infections. The most common application site reaction was application site burning, which occurred in 8%-26% of patients treated with ELIDEL Cream. 

      The following table depicts the incidence of adverse events pooled across the 2 identically designed 6-week studies with their open label extensions and the 1-year safety study for pediatric patients ages 2-17. Data from the adult active-controlled study is also included in this table. Adverse events are listed regardless of relationship to study drug.

Treatment Emergent Adverse Events (≥ 1%) in Elidel® Treatment Groups

	Pediatric Patients*Vehicle-Controlled(6 weeks)		Pediatric Patients*Open-Label (20 weeks)		Pediatric Patients*Vehicle-Controlled(1 year)		Adult ActiveComparator(1 year)
	Elidel® Cream (N=267) N (%)	Vehicle(N=136) N (%)	Elidel® Cream (N=335) N (%)		Elidel® Cream (N=272) N (%)	Vehicle(N=75) N (%)	Elidel® Cream(N=328)N (%)
At least 1 AE	182 (68.2%)	97 (71.3%)	240 (72.0%)		230 (84.6%)	56 (74.7%)	256 (78.0%)
Infections and Infestations
Upper Respiratory Tract Infection NOS	38 (14.2%)	18 (13.2%)	65 (19.4%)		13 (4.8%)	6 (8.0%)	14 (4.3%)
Nasopharyngitis	27 (10.1%)	10 (7.4%)	32 (19.6%)		72 (26.5%)	16 (21.3%)	25 (7.6%)
Skin Infection NOS	8 (3.0%)	9 (5.1%)	18 (5.4%)		6 (2.2%)	3 (4.0%)	21 (6.4%)
Influenza	8 (3.0%)	1 (0.7%)	22 (6.6%)		36 (13.2%)	3 (4.0%)	32 (9.8%)
Ear Infection NOS	6 (2.2%)	2 (1.5%)	19 (5.7%)		9 (3.3%)	1 (1.3%)	2 (0.6%)
Otitis Media	6 (2.2%)	1 (0.7%)	10 (3.0%)		8 (2.9%)	4 (5.3%)	2 (0.6%)
Impetigo	5 (1.9%)	3 (2.2%)	12 (3.6%)		11 (4.0%)	4 (5.3%)	8 (2.4%)
Bacterial Infection	4 (1.5%)	3 (2.2%)	4 (1.2%)		3 (1.1%)	0	6 (1.8%)
Folliculitis	3 (1.1%)	1 (0.7%)	3 (0.9%)		6 (2.2%)	3 (4.0%)	20 (6.1%)
Sinusitis	3 (1.1%)	1 (0.7%)	11 (3.3%)		6 (2.2%)	1 (1.3%)	2 (0.6%)
Pneumonia NOS	3 (1.1%)	1 (0.7%)	5 (1.5%)		0	1 (1.3%)	1 (0.3%)
Pharyngitis NOS	2 (0.7%)	2 (1.5%)	3 (0.9%)		22 (8.1%)	2 (2.7%)	3 (0.9%)
Pharyngitis Streptococcal	2 (0.7%)	2 (1.5%)	10 (3.0%)		0	<1%	0
Molluscum Contagiosum	2 (0.7%)	0	4 (1.2%)		5 (1.8%)	0	0
Staphylococcal Infection	1 (0.4%)	5 (3.7%)	7 (2.1%)		0	<1%	3 (0.9%)
Bronchitis NOS	1 (0.4%)	3 (2.2%)	4 (1.2%)		29 (10.7%)	6 (8.0%)	8 (2.4%)
Herpes Simplex	1 (0.4%)	0	4 (1.2%)		9 (3.3%)	2 (2.7%)	13 (4.0%)
Tonsillitis NOS	1 (0.4%)	0	3 (0.9%)		17 (6.3%)	0	2 (0.6%)
Viral Infection NOS	2 (0.7%)	1 (0.7%)	1 (0.3%)		18 (6.6%)	1 (1.3%)	0
Gastroenteritis NOS	0	3 (2.2%)	2 (0.6%)		20 (7.4%)	2 (2.7%)	6 (1.8%)
Chickenpox	2 (0.7%)	0	3 (0.9%)		8 (2.9%)	3 (4.0%)	1 (0.3%)
Skin Papilloma	1 (0.4%)	0	2 (0.6%)		9 (3.3%)	<1%	0
Tonsillitis Acute NOS	0	0	0		7 (2.6%)	0	0
Upper Respiratory Tract Infection Viral NOS	1 (0.4%)	0	3 (0.9%)		4 (1.5%)	0	1 (0.3%)
Herpes Simplex Dermatitis	0	0	1 (0.3%)		4 (1.5%)	0	2 (0.6%)
Bronchitis Acute NOS	0	0	0		4 (1.5%)	0	0
Eye Infection NOS	0	0	0		3 (1.1%)	<1%	1 (0.3%)
General Disorders and Administration Site Conditions
Application Site Burning	28 (10.4%)	17 (12.5%)	5 (1.5%)		23 (8.5%)	5 (6.7%)	85 (25.9%)
Pyrexia	20 (7.5%)	12 (8.8%)	41 (12.2%)		34 (12.5%)	4 (5.3%)	4 (1.2%)
Application Site Reaction NOS	8 (3.0%)	7 (5.1%)	7 (2.1%)		9 (3.3%)	2 (2.7%)	48 (14.6%)
Application Site Irritation	8 (3.0%)	8 (5.9%)	3 (0.9%)		1 (0.4%)	3 (4.0%)	21 (6.4%)
Influenza Like Illness	1 (0.4%)	0	2 (0.6%)		5 (1.8%)	2 (2.7%)	6 (1.8%)
Application Site Erythema	1 (0.4%)	0	0		6 (2.2%)	0	7 (2.1%)
Application Site Pruritus	3 (1.1%)	2 (1.5%)	2 (0.6%)		5 (1.8%)	0	18 (5.5%)
Respiratory, Thoracic and Mediastinal Disorders
Cough	31 (11.6%)	11 (8.1%)	31 (9.3%)		43 (15.8%)	8 (10.7%)	8 (2.4%)
Nasal Congestion	7 (2.6%)	2 (1.5%)	6 (1.8%)		4 (1.5%)	1 (1.3%)	2 (0.6%)
Rhinorrhea	5 (1.9%)	1 (0.7%)	3 (0.9%)		1 (0.4%)	1 (1.3%)	0
Asthma Aggravated	4 (1.5%)	3 (2.2%)	13 (3.9%)		3 (1.1%)	1 (1.3%)	0
Sinus Congestion	3 (1.1%)	1 (0.7%)	2 (0.6%)		<1%	<1%	3 (0.9%)
Rhinitis	1 (0.4%)	0	5 (1.5%)		12 (4.4%)	5 (6.7%)	7 (2.1%)
Wheezing	1 (0.4%)	1 (0.7%)	4 (1.2%)		2 (0.7%)	<1%	0
Asthma NOS	2 (0.7%)	1 (0.7%)	11 (3.3%)		10 (3.7%)	2 (2.7%)	8 (2.4%)
Epistaxis	0	1 (0.7%)	0		9 (3.3%)	1 (1.3%)	1 (0.3%)
Dyspnea NOS	0	0	0		5 (1.8%)	1 (1.3%)	2 (0.6%)
Gastrointestinal Disorders
Abdominal Pain Upper	11 (4.1%)	6 (4.4%)	10 (3.0%)		15 (5.5%)	5 (6.7%)	1 (0.3%)
Sore Throat	9 (3.4%)	5 (3.7%)	15 (5.4%)		22 (8.1%)	4 (5.3%)	12 (3.7%)
Vomiting NOS	8 (3.0%)	6 (4.4%)	14 (4.2%)		18 (6.6%)	6 (8.0%)	2 (0.6%)
Diarrhea NOS	3 (1.1%)	1 (0.7%)	2 (0.6%)		21 (7.7%)	4 (5.3%)	7 (2.1%)
Nausea	1 (0.4%)	3 (2.2%)	4 (1.2%)		11 (4.0%)	5 (6.7%)	6 (1.8%)
Abdominal Pain NOS	1 (0.4%)	1 (0.7%)	5 (1.5%)		12 (4.4%)	3 (4.0%)	1 (0.3%)
Toothache	1 (0.4%)	1 (0.7%)	2 (0.6%)		7 (2.6%)	1 (1.3%)	2 (0.6%)
Constipation	1 (0.4%)	0	2 (0.6%)		10 (3.7%)	<1%	0
Loose Stools	0	1 (0.7%)	4 (1.2%)		<1%	<1%	0
Reproductive System and Breast Disorders
Dysmenorrhea	3 (1.1%)	0	5 (1.5%)		3 (1.1%)	1 (1.3%)	4 (1.2%)
Eye Disorders
Conjunctivitis NEC	2 (0.7%)	1 (0.7%)	7 (2.1%)		6 (2.2%)	3 (4.0%)	10 (3.0%)
Skin & Subcutaneous Tissue Disorders
Urticaria	3 (1.1%)	0	1 (0.3%)		1 (0.4%)	<1%	3 (0.9%)
Acne NOS	0	1 (0.7%)	1 (0.3%)		4 (1.5%)	<1%	6 (1.8%)
Immune System Disorders
Hypersensitivity NOS	11 (4.1%)	6 (4.4%)	16 (4.8%)		14 (5.1%)	1 (1.3%)	11 (3.4%)
Injury and Poisoning
Accident NOS	3 (1.1%)	1 (0.7%)	1 (0.3%)		<1%	1 (1.3%)	0
Laceration	2 (0.7%)	1 (0.7%)	5 (1.5%)		<1%	<1%	0
Musculoskeletal, Connective Tissue and Bone Disorders
Back Pain	1 (0.4%)	2 (1.5%)	1 (0.3%)		<1%	0	6 (1.8%)
Arthralgias	0	0	1 (0.3%)		3 (1.1%)	1 (1.3%)	5 (1.5%)
Ear and Labyrinth Disorders
Earache	2 (0.7%)	1 (0.7%)	0		8 (2.9%)	2 (2.7%)	0
Nervous System Disorders
Headache	37 (13.9%)	12 (8.8%)	38 (11.3%)		69 (25.4%)	12 (16.0%)	23 (7.0%)

*Ages 2-17 years

      Two cases of septic arthritis have been reported in infants less than one year of age in clinical trials conducted with ELIDEL Cream (n = 2,443). Causality has not been established.

POST-MARKETING EVENTS

The following adverse reactions have been reported in patients using  ELIDEL Cream. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

General : Anaphylactic reactions, ocular irritation after application of the cream to the eye lids or near the eyes, angioneurotic edema, facial edema, skin flushing associated with alcohol use, skin discoloration  

Hematology/Oncology: Lymphomas, basal cell carcinoma, malignant melanoma, squamous cell carcinoma

REPORTS OF SIDE EFFECTS / ADVERSE REACTIONS RELATED TO ELIDEL

Possible Elidel side effects / adverse reactions in 10 year old female

Reported by a physician from Belgium on 2007-01-16

Patient: 10 year old female weighing 25.1 kg (55.2 pounds)

Reactions: Hodgkin's Disease Mixed Cellularity Stage I Supradiaphragmatic, Lymphadenopathy, Asthenia, Infectious Mononucleosis

Suspect drug(s):
Elidel
    Dosage: 30 g
    Administration route: Topical
    Indication: Dermatitis Atopic
    Start date: 2003-06-01

Elidel
    Dosage: 30 g
    Administration route: Topical
    Start date: 2004-04-01
    End date: 2004-06-01

Other drugs received by patient: Desonide

Possible Elidel side effects / adverse reactions in 8 month old male

Reported by a individual with unspecified qualification from United States on 2007-01-18

Patient: 8 month old male weighing 11.3 kg (24.9 pounds)

Reactions: Abdominal Pain, Viral Rash, Weight Decreased, Ear Tube Insertion, Pyrexia, Erythema, Otorrhoea, Pharyngitis Streptococcal, Staphylococcal Bacteraemia, Crying, Blister, Respiratory Rate Increased, Stomatitis, Pain in Extremity, Pancytopenia, Abnormal Behaviour, Insomnia, Anorexia, Ear Pain, Neutropenia, Pain, Chills, Central Line Infection, Sinusitis, White Blood Cell Count Decreased, Ear Discomfort, Vomiting, Retching, Drug Hypersensitivity, Ear Infection, Rash, Discomfort, Acute Lymphocytic Leukaemia, Mucosal Inflammation, Diarrhoea, Joint Sprain, Dysuria, Heart Rate Increased, Viral Pharyngitis, Gait Disturbance

Adverse event resulted in: hospitalization

Suspect drug(s):
Elidel

Other drugs received by patient: Elocon; Atarax

Possible Elidel side effects / adverse reactions in 39 year old female

Reported by a physician from Spain on 2007-01-19

Patient: 39 year old female

Reactions: White Blood Cell Count Decreased, Malignant Melanoma in Situ, Surgery, Melanocytic Naevus

Suspect drug(s):
Elidel
    Administration route: Topical
    Indication: Dermatitis Atopic
    Start date: 2004-01-01

Elidel
    Administration route: Topical
    Start date: 2005-04-01